Shortage of plasma-derived medicinal products: what is next? narrative literature review on its causes and counteracting policies in Italy.

Introduction: This paper describes the peculiarities of the plasma-derived medicinal product (PDMP) market and illustrates the results of a review of the literature on policies aimed at counteracting the shortage of PDMPs. Characteristics of PDMPs: Plasma is primarily used for the industrial production of blood products (80%). The demand for PDMPs, particularly immunoglobulins (IGs), is increasing. However, the production of PDMPs is complex, long (7-12 months), and expensive, accounting, according to US estimates, for 57% of the total costs of PDMPs compared to 14% for small molecules. PDMP market: Unexpected increases in clinical need cannot be addressed in the short term. Once the demand for some diseases is satisfied, the collection and fractionation of plasma will only be used to supply some specific patients. Hence, the full weight of the marginal costs, which remain constant, are borne by a few products. According to last liter economics, the industry stops producing when the marginal revenue equals the marginal cost, thereby reducing the convenience of producing the most commonly used PDMPs (albumin and IG). The imbalance between the demand and supply of PDMPs was exacerbated by the COVID-19 pandemic, which further increased the cost of plasma collection. Shortage issue and possible solutions: Policies to counteract this imbalance have also been discussed. If the demand is inappropriate, it should be reduced. If the demand is appropriate and supply cannot be increased, the demand should be prioritized for patients for whom PDMPs are the only available treatment. If the shortage depends on insufficient supply and technical and allocative efficiency, both production and supply should be improved, together with incentives for all stakeholders involved in the PDMP market to increase the sustainability of production/supply. The paper is focused on this second issue, that is supply-driven unbalance.

[Medico-legal and management issues in patient blood management era.] / Aspetti medico-legali e organizzativi nell'era del Patient blood management.

In recent decades, the approach to blood transfusion has changed radically around the world. In the past, transfusion represented the only solution for anemia, today the paradigm has changed: through the implementation of the Patient blood management (Pbm) program it is possible to manage the patient's own blood in order to reduce and, in many cases, eliminate the administration of blood components for transfusion. This approach increases patient safety by reducing clinical risks as well as costs. The implementation of the PBM program in Australia has demonstrated that the use of blood is not strictly necessary but, on the contrary, is largely avoidable. Through change management the traditional attitude of doctors and healthcare facilities can be modified. Law no. 24/2017 focuses on the safety of care by encouraging the necessary implementation of Pbm in hospital settings; the failure to adopt an organized Pbm program may constitute, in the event of an adverse transfusion event, a clear profile of health responsibility on the part of the management and clinicians.

Women Living with HIV in Italian Prison Settings: Results from the Gender-Specific ROSE Network.

BACKGROUND: Incarcerated women are a minority in the Italian prison population. The lack of prevention and awareness of HIV infection and the lack of access to treatment make the treatment path difficult. METHODS: we conducted a multi-center study including incarcerated women living with HIV (WLWH). RESULTS: The study included 85 WLWH with a mean age of 41.7 ± 8.7 years, and 58.8% (50/85) of them were Italian. Principally, HIV transmission was related to sexual intercourse, 47% of all patients were PWIDs, and 62.5% of them were on opioid substitution therapy (OST). Overall, 56.4% of the included patients had a CD4+ cell count of >500 cells/mmc. Among the participants, 92.9% were on antiretroviral therapy, 87.3% had treatment before incarceration, and 83.5% were virologically suppressed. Among the 13 non-virally-suppressed patients, 53.8% were unaware of their serological status before incarceration and had started HAART but were still not virologically suppressed; 46.2% (6/13) had a lack of compliance or had suspended the treatment before incarceration and restarted it after admission. All patients with chronic hepatitis C underwent treatment with direct-acting antivirals and reached a sustained virological response. CONCLUSIONS: the detention of these women could represent an occasion for the patients' healthcare provision and use, and the creation of a gender-specific network can be an effective strategy for reaching this population.

Main Predictors of COVID-19 Vaccination Uptake among Italian Healthcare Workers in Relation to Variable Degrees of Hesitancy: Result from a Cross-Sectional Online Survey.

Background: Hesitancy remains one of the major hurdles to vaccination, regardless of the fact that vaccines are indisputable preventive measures against many infectious diseases. Nevertheless, vaccine hesitancy or refusal is a growing phenomenon in the general population as well as among healthcare workers (HCWs). Many different factors can contribute to hesitancy to COVID-19 vaccination in the HCWs population, including socio-demographic characteristics (female gender, low socio-economical status, lower age), individual beliefs regarding vaccine efficacy and safety, as well as other factors (occupation, knowledge about COVID-19, etc.). Understanding the determinants of accepting or refusing the COVID-19 vaccination is crucial to plan specific interventions in order to increase the rate of vaccine coverage among health care workers. Methods: We conducted a cross-sectional online survey on HCWs in seventeen Italian regions, between 30 June and 4 July 2021, in order to collect information about potential factors related to vaccine acceptance and hesitancy. Results: We found an overall vaccine uptake rate of 96.4% in our sample. Acceptance was significantly related to job task, with physicians showing the highest rate of uptake compared to other occupations. At univariate analysis, the HCWs population's vaccine hesitancy was significantly positively associated with fear of vaccination side effects (p < 0.01), and negatively related to confidence in the safety and efficacy of the vaccine (p < 0.01). Through multivariate analysis, we found that only the fear of possible vaccination side effects (OR: 4.631, p < 0.01) and the confidence in vaccine safety and effectiveness (OR: 0.35 p < 0.05) remained significantly associated with hesitancy. Conclusion: Action to improve operator confidence in the efficacy and safety of the vaccine should improve the acceptance rate among operators.

Protection of Prisoners with Mental Health Disorders in Italy: Lights and Shadows after the Abolition of Judicial Psychiatric Hospitals.

In Italy, a person suffering from a mental disorder who commits a crime will be given a custodial security order and serve the period of admission at a Residenza per la esecuzione delle misure di sicurezza (REMS) (Residence for the Execution of Security Measures, hereinafter "REMS"). These institutions have been established recently and though equipped with the necessary safety measures, the focus is on psychiatric therapy. Despite being present on a national scale, access is very limited in terms of capacity. Immediate remedial measures are needed, so much so that the European Court of Human Rights recently condemned Italy for this very reason. This article, through a review of the constitutive principles of these institutions, shows how they have very positive aspects such as the attention to necessary psychotherapy in order to protect the right to health and the real taking charge of the fragility of the subjects; however, it is seen how there are many negative aspects linked above all to the scarce availability of places in these structures. The article provides suggestions on a more comprehensive strategy for facilities for detainees with mental disorders.

HCV spread among female incarcerated population and treatment pathways to viral elimination in Italian prison settings: clinical perspectives and medico legal aspects.

BACKGROUND: Hepatitis C virus (HCV) infection is more frequent among incarcerated people than in general population. In the DAAs era, the short schedules and the low risk of adverse reactions, increased the number of HCV treatments. However, the most part of literature reports lack of incarcerated women inclusion in studies on field. Our aim is to assess the screening execution, HCV prevalence, and DAAs treatment among incarcerated women. A focused insight on quick vs standard diagnosis and staging approach will be also provided. METHODS: Incarcerated women from 4 Italian regions' penitentiary institutes were included. HCV screening was executed with HCV saliva test (QuickOral Test®) or phlebotomy. Stage of liver fibrosis was evaluated with FIB-4 value or fibroscan®, based on physicians' decision. Treatment prescription followed national protocols. RESULTS: We included 156 women, 89 (57%) were Italian, mean age was 41 ± 10 years, and 28 (17.9%) were people who inject drugs (PWIDs). Overall, the HCV seroprevalence was 20.5%. Being PWID and on opioid substitution therapy (OST) were significantly associated with serological status (p-value < 0.001). Of them, the 75.5% of patients had active infection, the most frequent genotype was 3a (50%). Among them, 4 (16.6%) and 6 (25%) had psychosis or alcohol abuse history. The 62.5%, 25% and 12.5% had low, intermediate, and advanced fibrosis, respectively. Out of the 24 HCV-RNA positive patients, the 75% underwent to DAAs treatment. The sustained virological response (SVR12) was achieved in 88.8% of cases. When evaluating the influence of quick diagnosis and staging methods vs standard phlebotomy and fibroscan® on SVR12, FIB-4 use showed higher performance for retainment in treatment during prison staying (p = 0.015), while the use of quick saliva test had no influence on the outcome (p = 0.22). CONCLUSION: HCV seroprevalence and active infections are very high among incarcerated women. More tailored interventions should be focused on HCV diagnosis and treatment in female prison population. The use of quick staging methods (FIB-4) is useful to increase SVR12 achievement without delays caused by the fibroscan® awaiting.

Guiding Principles for Surgical Pathways: A Tool for Improving Outcomes and Patient Safety.

Surgical activity is an important aspect for the management of health and safety processes and from an organizational perspective is one of the most complex activities performed in hospitals. It is often a defining and high value feature for any healthcare facility while being one of the most high-risk procedures for patients with the highest number of avoidable adverse events. To ensure effective management of surgical pathways, they need to be considered from the perspective of clinical governance which takes a global approach to planning and management with the goal of improving safety and quality for patients. This paper contains the main features of this objective outlined within the document issued subsequent to the State-Regional Italian Government conference. This regulatory effort includes effective recommendations to make surgical pathways safer and more efficient with particular reference to lean management, patient blood management and patient safety.

Health and Economic Impact of Atrial Fibrillation of Workers in Italy: Social Security Benefits.

BACKGROUND: The aim of this research was to analyze trends in social security applications in Italy as a result of the onset of atrial fibrillation, analyzing data pertaining to the classification of professions and assessing the economic impact on the social security system. METHODS: We analyzed all applications for invalidity allowances and invalidity pensions throughout Italy over a 10-year period from 01.01.2009 to 31.12.2019, giving specific attention to all reports indicating atrial fibrillation as the principal diagnosis (Cod. ICD-9-CM 427.31). We then extracted the relative expenditure data for said benefits. The results of all analyses have been collated in tables. RESULTS: Over the period in question, a total of 3468 applications for assistance were filed throughout Italy indicating a diagnosis of atrial fibrillation, of which 58% were rejected, 41% qualified for an invalidity allowance, and only 1.1% qualified for a pension. On average, every year, 1100 workers received social security benefits as a result of a diagnosis of atrial fibrillation, which equates to an average annual expenditure of EUR 10 million. A comparison of the data from the first observation year (2009) with data from the last (2019) shows a rising trend in the number of beneficiaries and consequently in expenses. CONCLUSIONS: The social security assistance provided by the Italian government by means of the National Institute of Social Security is fundamental to social cohesion and to those who are either permanently disabled from working or those with a significantly diminished earning capacity. This assistance is associated with a significant financial cost, which requires careful monitoring.

Pharmacological Abortion in a Pandemic: An Italian Medico-Legal Perspective.

The limitations caused by the spread of the SARS-CoV2 virus have had repercussions on the voluntary termination of pregnancy. During the pandemic, Italy issued updated guidelines regarding voluntary termination of pregnancy by means of mifepristone and prostaglandin. This included news concerning the time limit and location in which this procedure could be accessed: updates partially recognize women's needs, and they are into line with the European parliament's recent exhortations. However, these updates do not change the previously provided responsibilities that lie with doctors. This article aimed to compare regulations concerning medical abortion in Italy and other countries, with a focus on recent Italian updates in the context of pandemic.

Health in Prison: Does Penitentiary Medicine in Italy Still Exist?

Despite the detailed legislative developments that have occurred within the context of prison medicine in Italy, problems of a management nature continue to affect prisoner health and management, which in turn impact the prison system's ability to offer prisoners a real opportunity for rehabilitation. Certain behavioral aspects reported in prisons may alter and negatively impact the normal doctor-patient relationship, including elements that hinder the therapeutic alliance and impede proper clinical risk prevention and management. However, practical steps may be taken in connection with the analysis of flows and healthcare services that may enable prison administrations to bring about a true, modern restructure of the prison system.

Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects.

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.

Organizational Strategies for the Management of Intravenous Iron Therapy in Non-Hospitalized Settings: A Safe Opportunity to Implement Patient Blood Management in Italy.

This article analyzes the recommendations issued by the Emilia Romagna region in July 2020 on "Organizational strategies for the safe management of intravenous iron therapy in patients in non-hospitalized settings". The objective of these recommendations is to set up safe intravenous iron administration sites outside the hospital environment across the national territory. The document facilitates the organization of methods for intravenous iron infusion that are safe for the patient and correct from a medico-legal perspective. In addition, it opens the way for the widespread use of iron infusion in the field, providing benefits to patient quality of life. This program prevents unnecessary transfusions, reduces costs, prevents overcrowding in hospitals in the event of a pandemic, and enables patient treatment in the field, thus, saving on the use of personnel.

An Analysis of the Social and Economic Costs of Breast Cancer in Italy.

BACKGROUND: Breast cancer is the most prevalent cancer affecting women and it represents an important economic burden. The aim of this study was to estimate the socio-economic burden of breast cancer (BC) in Italy both from the National Health Service (NHS) and the government perspectives (costs borne by the social security system). METHODS: The economic analysis was based on the costs incurred by the NHS from 2008 to 2016 (direct costs related to hospitalizations) and by the National Social Security Institute (INPS) from 2009 to 2015 (costs of social security benefits) for patients with breast cancer. The analysis was based on the Hospital Information System (HIS) and Disability Insurance Awards databases. For both databases, patients affected by a malignant neoplasm of the female breast, carcinoma in situ, or secondary malignant neoplasm of the breast were considered. RESULTS: Results show that more than 75,000 women were hospitalized for breast cancer every year, with an overall cost for hospitalization of about €300 million per year. From the Social Security analysis, a number of 29,000 beneficiaries each year was estimated. Considering per patient social costs, breast cancer at the primary stage cost €8828 per year, while secondary neoplasms cost €9780, with an average total economic burden of €257 million per year. CONCLUSIONS: This analysis focused on the economic impact of breast cancer in Italy, showing that an advanced stage of the disease was associated with a higher cost.

First Dose of the BNT162b2 mRNA COVID-19 Vaccine Reduces Symptom Duration and Viral Clearance in Healthcare Workers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than one hundred million people since the beginning of the worldwide pandemic. In this study, data from a large hospital in central Italy was used to evaluate the impact of the first dose of the BNT162b2 mRNA vaccine on SARS-CoV-2 infections in terms of the prevalence of symptomatic cases, symptom duration, and viral clearance timing. All vaccinated Healthcare Workers (HCWs) with positive RT-PCR by nasopharyngeal (NP) swabs were divided into two cohorts (positive RT-PCR within day 12 and positive RT-PCR between day 13 and day 21 after first dose administration) and compared for the presence and duration of symptoms and the timing of viral clearance. The same variables were evaluated across HCWs with positive RT-PCR within 6 days after first dose administration and non-vaccinated HCWs with positive RT-PCR between 1 October 2020 and 28 February 2021. Eighteen HCWs tested positive on RT-PCR by NP swab from day 1 to day 12 after the 1st dose administration (incidence rate 6.2 × 10-4) and 5 HCWs from day 13 to day 21 (incidence rate 2.3 × 10-4). Symptom duration and viral clearance timing are significantly shorter in the cohort of HCWs with positive RT-PCR 12 days after the first dose of the BNT162b2 mRNA vaccine. The administration of the first dose proved effective in reducing presence, symptom duration, and viral clearance even in HCWs vaccinated for less than 6 days. These results could have implications on public health and post-exposure prophylaxis.

Evaluation of Immunity for Mumps among Vaccinated Medical Students.

Healthcare workers are considered at higher risk for mumps infection than the general population. Since 2017, the national immunization plan recommended the administration of a dose of measles-mumps-rubella (MMR) vaccine to the healthcare operators who are unable to demonstrate a complete vaccination history or that are seronegative for at least one of the three agents. Regarding mumps infection, based on actual concerns regarding the loss of protection over the years after vaccination, the Advisory Committee on Immunization Practices (ACIP) recommended to administer a third dose of vaccine to operators previously vaccinated with two doses of MMR vaccine who belong to a group at increased risk of mumps infection in the event of an epidemic. This guideline, however, is not currently followed in Italy, resulting in a potential risk for vaccinated operators to become unprotected from mumps over the years. The aim of our study is to evaluate the persistence of a protective antibody level for mumps among medical students vaccinated during infancy or adolescence, at the start of their hospital internship. We retrospectively evaluated mumps-specific IgG levels in a group of medical students, in the period from 1 January to 31 December 2020. We evaluated the persistence of the detectable level of mumps-specific antibodies in relation to their vaccinal status, gender and time elapsed from vaccination. We found that 17.4% (65 subjects) of our sample were seronegative for mumps. The univariate analysis showed a significant difference in serological protection between male and female gender (77.0% vs. 86.2%; p < 0.05 with chi2 test) and between age classes (86.5% vs. 76.4%; p < 0.05 for subjects aged 18-23 years and over 23 years, respectively). Female gender was significantly related to higher serological protection even after adjusting for age classes and number of vaccine doses administered in a multivariate analysis model. Our study shows a substantial percentage of subjects lacking a protective mumps titer among medical students who were vaccinated in childhood. Given the higher risk of infection among those subjects, routine pre-employment screening should be performed among those operators regardless of their vaccination history and a third dose of MMR should be offered to unprotected students.

COVID-19 Pandemic and Equal Access to Vaccines.

The COVID-19 pandemic has evidenced the chronic inequality that exists between populations and communities as regards global healthcare. Vaccination, an appropriate tool for the prevention of infection, should be guaranteed by means of proportionate interventions to defeat such inequality in populations and communities affected by a higher risk of infection. Equitable criteria of justice should be identified and applied with respect to access to vaccination and to the order in which it should be administered. This article analyzes, as regards the worldwide distribution of anti-COVID-19 vaccines, the various ways the principle of equity has been construed and applied or even overlooked. The main obstacle to equal access to vaccines is vaccine nationalism. The perception of equity varies with the differing reference values adopted. Adequate response to needs appears to be the principal rule for achieving the criterion of equity in line with distributive justice. Priorities must be set equitably based on rational parameters in accordance with current needs. The entire process must be governed by transparency, from parameter identification to implementation. The issue of equal access to vaccination affects the entire world population, necessitating specific protective interventions. In light of this, the World Health Organization (WHO) has devised the COVAX plan to ensure that even the poorest nations of the world receive the vaccine; certain initiatives are also supported by the European Union (EU). This pandemic has brought to the fore the need to build a culture of equitable relationships both in each country's own domain and with the rest of the world.

Intention to Be Vaccinated for COVID-19 among Italian Nurses during the Pandemic.

BACKGROUND: While the COVID-19 pandemic has spread globally, health systems are overwhelmed by both direct and indirect mortality from other treatable conditions. COVID-19 vaccination was crucial to preventing and eliminating the disease, so vaccine development for COVID-19 was fast-tracked worldwide. Despite the fact that vaccination is commonly recognized as the most effective approach, according to the World Health Organization (WHO), vaccine hesitancy is a global health issue. METHODS: We conducted a cross-sectional online survey of nurses in four different regions in Italy between 20 and 28 December 2020 to obtain data on the acceptance of the upcoming COVID-19 vaccination in order to plan specific interventions to increase the rate of vaccine coverage. RESULTS: A total of 531 out of the 5000 nurses invited completed the online questionnaire. Most of the nurses enrolled in the study (73.4%) were female. Among the nurses, 91.5% intended to accept vaccination, whereas 2.3% were opposed and 6.2% were undecided. Female sex and confidence in vaccine efficacy represent the main predictors of vaccine intention among the study population using a logistic regression model, while other factors including vaccine safety concerns (side effects) were non-significant. CONCLUSIONS: Despite the availability of a safe and effective vaccine, intention to be vaccinated was suboptimal among nurses in our sample. We also found a significant number of people undecided as to whether to accept the vaccine. Contrary to expectations, concerns about the safety of the vaccine were not found to affect the acceptance rate; nurses' perception of vaccine efficacy and female sex were the main influencing factors on attitudes toward vaccination in our sample. Since the success of the COVID-19 immunization plan depends on the uptake rate, these findings are of great interest for public health policies. Interventions aimed at increasing employee awareness of vaccination efficacy should be promoted among nurses in order to increase the number of vaccinated people.